Abstract: Objective To access the clinical performance of detecting fecal SEPT-9 and miRNA-34b/c gene methylation for colorectal tumor screening in patients diagnosed with colorectal tumor. Methods In this case-control study, the fecal SEPT-9 and miRNA-34b/c gene methylation in patients diagnosed with colorectal cancer（n = 35）,colorectal adenoma（n = 47） and normal controls （n = 52） was identified by by using methylation-sensitive high-resolution melting （MS-HRM） to access the clinical performance for colorectal tumor screening. Results The methylation rates of fecal SEPT-9 and miRNA-34b/c detection in the colorectal cancer group were 68.6% and 71.4%, 57.4% and 63.8% in the colorectal adenoma group, and 9.6% and 11.5% in normal control group, respectively. The methylation rates of SEPT-9 and miRNA-34b/c significantly differed among three groups （²_SEPT-9 = 37.185, ²_miRNA-34b/c = 40.040, all P < 0.001）. According to two-group comparison by using Bonferroni correction,the methylation rates did not significantly differ between the colorectal cancer and colorectal adenoma groups （both P > 0.05）, which significantly differed from those in the normal control group （all P < 0.001）. The methylation rates of combined detection of SEPT-9 and miRNA-34b/c were 88.6% in the colorectal cancer group, 76.6% in the colorectal adenoma group and 13.5% in normal control group. Combined decection methylation rates of SEPT-9 and miRNA-34b in colorectal cancer group and colorectal adenoma group were significantly higher compared with that of either SEPT-9 or miRNA-34b/c alone （all P < 0.05）. Conclusions Detecting fecal SEPT-9 and miRNA-34b/c gene methylation yields high clinical performance for colorectal tumor screening. Methylated SEPT-9 and miRNA-34b/c genes may be a new panel of biomarkers for colorectal tumor screening in large-scale population. The performance of combined detection of multi-gene methylation detection is better compared with that of single gene.